We have previously determined amino acid sequences of human, mouse, rat and bovine retinal S-antigen and rat pineal gland S-antigen. Immunogenic sites and four uveitopathogenic sites of S-antigen were also determined. Two of the immunogenic sequences were highly conserved among these species. There are many proteins which have a similar sequence with a uveitopathogenic site in the National Biomedical Research Foundation data base. We chemically synthesized many peptides, some of which induced experimental autoimmune uveitis (EAU) and experimental autoimmune pinealitis (EAP) in Lewis rats, including synthetic peptides from yeast (Saccharomyces cerevisiae) histone H3, Escherichia coli hypothetical protein, potato proteinase inhibitor, hepatitis virus protein, Moloney murine sarcoma virus protein, and Moloney murine leukemia virus protein. In addition, native yeast histone H3 was also capable of inducing EAU. Interestingly, the animals that were administered the yeast histone orally suppressed the EAU and EAP induction by either yeast histone H3 peptide or a S-antigen peptide. Thus, the peptides that have molecular mimicry cross-induced the tolerance. These findings provide a basis for autoimmune inflammatory diseases of the eye in humans.